Developments in methods of immunomodulation of nonhuman primates undergoing pig organ transplantation during the past 12 to 18 months are reviewed in the light of previous studies. Depletion of xenoreactive (anti-Gal) antibodies can be achieved successfully by several techniques, thereby preventing hyperacute rejection; however, continuing production of antibody remains a problem. The pharmacologic agents currently available have proved inadequate in preventing the eventual development of acute vascular or delayed xenograft rejection. However, good function of one orthotopically-transplanted pig heart in a baboon for 39 days suggests that pig hearts will be able to support life in primates for long periods if the immune barriers can be overcome. The ability of therapy with an anti-CD154 monoclonal antibody to completely prevent the induced antibody response to transplanted pig cells and organs is an encouraging step forward. An anti-B-cell monoclonal antibody that depleted all B cells failed to prevent continuing antibody production, indicating that plasma cells, rather than B cells, are probably the major source of these antibodies. Some progress has been made; however, in the absence of a genetically modified pig that does not express Gal epitope, it may be necessary to direct attention toward suppression of plasma cell function.